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Cerebral small vessel disease related to a heterozygous missense mutation in HTRA1: A case report
Yuanyan Gao1, Yumin Zheng1, Jieren Lian2
1Department of Neurology, Shanghai Civil Aviation Hospital-Ruijin Hospital Gubei Branch, Shanghai, China.
Rationale:
Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy is a rare genetic condition classified as a cerebral small vessel disease (CSVD). Traditionally, this disorder has been linked to either homozygous or compound heterozygous mutations in the high-temperature requirement A serine peptidase 1 (HTRA1) gene. Nevertheless, contemporary research has uncovered that heterozygous mutations in HTRA1 can also manifest in patients displaying patterns of autosomal dominant inheritance. In order to explore the association between the types of HTRA1 gene mutations and the genetic pattern of CSVD, in this case report, we identified a case of autosomal dominant hereditary CSVD due to a new heterozygous mutation of the HTRA1 gene in an Asian female.
Patient Concerns:
The patient experienced a later onset of cognitive disorder and gait disturbances, and notably, there was an absence of alopecia and spondylosis, which are commonly observed extra-neurological features associated with cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy. Neuroimaging conducted through magnetic resonance imaging revealed extensive white matter lesions and microbleeds localized within the brainstem and both cerebral hemispheres. Utilizing next-generation sequencing techniques, a novel heterozygous missense mutation in the HTRA1 gene (c.524 T>A:p.V175E) was identified.
Diagnoses:
The patient was diagnosed as HTRA1-related autosomal dominant CSVD.
Interventions:
The patient was treated with donepezil and quetiapine because of the memory impairments and visual hallucination in the early stage of the disease course. After the diagnosis of CSVD and the clinical manifestations of depressive tendencies, we treated her with Cilostazol and Sertraline additionally.
Outcomes:
The patient symptoms were relieved temporarily. As the disease progresses, the patient experienced 2 episodes of epilepsy and 1 cerebral infarction event.
Lessons:
This case suggests that individuals with the heterozygous HTRA1 mutation at V175E may also present clinical characteristics consistent with hereditary CSVD, expanding the recognized spectrum of HTRA1 mutations related to autosomal dominant small vessel disease.
